Purpose – purpose of this article is to report about the progress of the development of a method that makes sense of knowledge productivity, in order to be able to give direction to knowledge management initiatives. Methodology/approach – the development and testing of the method is based on the paradigm of the Design Sciences. In order to increase the objectivity of the research findings, and in order to test the transferability of the method, this article suggests a methodology for beta testing. Findings – based on the experiences within this research, the concept of beta testing seems to fit Design Science Research very well. Moreover, applying this concept within this research resulted in valuable findings for further development of the method. Research implications – this is the first article that explicitly applies the concept of beta testing to the process of developing solution concepts. Originality/value – this article contributes to the further operationalization of the relatively new concept of knowledge productivity. From a methodological point of view, this article aims to contribute to the paradigm of the Design Sciences in general, and the concept of beta testing in particular.
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There remains some debate about whether beta power effects observed during sentence comprehension reflect ongoing syntactic unification operations (beta-syntax hypothesis), or instead reflect maintenance or updating of the sentence-level representation (beta-maintenance hypothesis). In this study, we used magnetoencephalography to investigate beta power neural dynamics while participants read relative clause sentences that were initially ambiguous between a subject- or an object-relative reading. An additional condition included a grammatical violation at the disambiguation point in the relative clause sentences. The beta-maintenance hypothesis predicts a decrease in beta power at the disambiguation point for unexpected (and less preferred) object-relative clause sentences and grammatical violations, as both signal a need to update the sentence-level representation. While the beta-syntax hypothesis also predicts a beta power decrease for grammatical violations due to a disruption of syntactic unification operations, it instead predicts an increase in beta power for the object-relative clause condition because syntactic unification at the point of disambiguation becomes more demanding. We observed decreased beta power for both the agreement violation and object-relative clause conditions in typical left hemisphere language regions, which provides compelling support for the beta-maintenance hypothesis. Mid-frontal theta power effects were also present for grammatical violations and object-relative clause sentences, suggesting that violations and unexpected sentence interpretations are registered as conflicts by the brain's domain-general error detection system.
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The relationship between the evoked responses (ERPs/ERFs) and the event-related changes in EEG/MEG power that can be observed during sentence-level language comprehension is as yet unclear. This study addresses a possible relationship between MEG power changes and the N400m component of the event-related field. Whole-head MEG was recorded while subjects listened to spoken sentences with incongruent (IC) or congruent (C) sentence endings. A clear N400m was observed over the left hemisphere, and was larger for the IC sentences than for the C sentences. A time-frequency analysis of power revealed a decrease in alpha and beta power over the left hemisphere in roughly the same time range as the N400m for the IC relative to the C condition. A linear regression analysis revealed a positive linear relationship between N400m and beta power for the IC condition, not for the C condition. No such linear relation was found between N400m and alpha power for either condition. The sources of the beta decrease were estimated in the LIFG, a region known to be involved in semantic unification operations. One source of the N400m was estimated in the left superior temporal region, which has been related to lexical retrieval. We interpret our data within a framework in which beta oscillations are inversely related to the engagement of task-relevant brain networks. The source reconstructions of the beta power suppression and the N400m effect support the notion of a dynamic communication between the LIFG and the left superior temporal region during language comprehension.
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Oscillatory neural dynamics have been steadily receiving more attention as a robust and temporally precise signature of network activity related to language processing. We have recently proposed that oscillatory dynamics in the beta and gamma frequency ranges measured during sentence-level comprehension might be best explained from a predictive coding perspective. Under our proposal we related beta oscillations to both the maintenance/change of the neural network configuration responsible for the construction and representation of sentence-level meaning, and to top-down predictions about upcoming linguistic input based on that sentence-level meaning. Here we zoom in on these particular aspects of our proposal, and discuss both old and new supporting evidence. Finally, we present some preliminary magnetoencephalography data from an experiment comparing Dutch subject- and object-relative clauses that was specifically designed to test our predictive coding framework. Initial results support the first of the two suggested roles for beta oscillations in sentence-level language comprehension.
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In this study, we used electroencephalography to investigate the influence of discourse-level semantic coherence on electrophysiological signatures of local sentence-level processing. Participants read groups of four sentences that could either form coherent stories or were semantically unrelated. For semantically coherent discourses compared to incoherent ones, the N400 was smaller at sentences 2–4, while the visual N1 was larger at the third and fourth sentences. Oscillatory activity in the beta frequency range (13–21 Hz) was higher for coherent discourses. We relate the N400 effect to a disruption of local sentence-level semantic processing when sentences are unrelated. Our beta findings can be tentatively related to disruption of local sentence-level syntactic processing, but it cannot be fully ruled out that they are instead (or also) related to disrupted local sentence-level semantic processing. We conclude that manipulating discourse-level semantic coherence does have an effect on oscillatory power related to local sentence-level processing.
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This colomn is the sequel of the colomn Beta talent forward. In this colomn the central question is how our autistiform beta talent candidates can use their powers as part of the "tribe", so that they reinforce the team 's intelligence.
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Penicillin acylase (PA) from Escherichia coli can catalyze the coupling of an acyl group to penicillin- and cephalosporin-derived beta-lactam nuclei, a conversion that can be used for the industrial synthesis of beta-lactam antibiotics. The modest synthetic properties of the wild-type enzyme make it desirable to engineer improved mutants. Analysis of the crystal structure of PA has shown that residues alphaR145 and alphaF146 undergo extensive repositioning upon binding of large ligands to the active site, suggesting that these residues may be good targets for mutagenesis aimed at improving the catalytic performance of PA. Therefore, site-saturation mutagenesis was performed on both positions and a complete set of all 38 variants was subjected to rapid HPLC screening for improved ampicillin synthesis. Not less than 33 mutants showed improved synthesis, indicating the importance of the mutated residues in PA-catalyzed acyl transfer kinetics. In several mutants at low substrate concentrations, the maximum level of ampicillin production was increased up to 1.5-fold, and the ratio of the synthetic rate over the hydrolytic rate was increased 5-15-fold. Moreover, due to increased tendency of the acyl-enzyme intermediate to react with beta-lactam nucleophile instead of water, mutants alphaR145G, alphaR145S and alphaR145L demonstrated an enhanced synthetic yield over wild-type PA at high substrate concentrations. This was accompanied by an increased conversion of 6-APA to ampicillin as well as a decreased undesirable hydrolysis of the acyl donor. Therefore, these mutants are interesting candidates for the enzymatic production of semi-synthetic beta-lactam antibiotics.
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After more than a year in our Beta talent project, a characteristic of the (autistic) candidates seems to be more common than any other: a lack of confidence in working in teams. The project is intended for people within the autistic spectrum with excellent (cognitive) competencies, who nevertheless cannot find or keep a job. At first I was inclined to view the problem primarily as a problem of the current social structure of labour. Admittedly, many candidates are original thinkers who are not always willing to let go of their own way of thinking to go along with those of others. At the same time, using the power of teamwork has become much more prominent today than ever before....
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The role of neuronal oscillations during language comprehension is not yet well understood. In this paper we review and reinterpret the functional roles of beta- and gamma-band oscillatory activity during language comprehension at the sentence and discourse level. We discuss the evidence in favor of a role for beta and gamma in unification (the unification hypothesis), and in light of mounting evidence that cannot be accounted for under this hypothesis, we explore an alternative proposal linking beta and gamma oscillations to maintenance and prediction (respectively) during language comprehension. Our maintenance/prediction hypothesis is able to account for most of the findings that are currently available relating beta and gamma oscillations to language comprehension, and is in good agreement with other proposals about the roles of beta and gamma in domain-general cognitive processing. In conclusion we discuss proposals for further testing and comparing the prediction and unification hypotheses.
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Glucocorticoids (GCs), such as prednisolone (PRED), are widely prescribed anti-inflammatory drugs, but their use may induce glucose intolerance and diabetes. GC-induced beta cell dysfunction contributes to these diabetogenic effects through mechanisms that remain to be elucidated. In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to reduce the phosphorylation of PERK and its downstream substrate eIF2α. These modulations of ER stress pathways were accompanied by upregulation of calpain 10 and increased cleaved caspase 3, indicating that long term exposure to PRED ultimately promotes apoptosis. Taken together, our data suggest that the inhibition of insulin biosynthesis by PRED in the insulin-secreting INS-1E cells results, at least in part, from a GR-mediated impairment in ER homeostasis which may lead to apoptotic cell death.
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